The long term objectives of this research are to test, in vivo, the influence of the microenvironment on axonal regeneration in the mouse peripheral nervous system. We will continue to develop anatomic and physiologic methods and techniques which will quantitatively assess functional as well as anatomical recovery following peripheral nerve repair. Specific Aims I and II will quantify the regeneration response of sensory and motor neurons and their axons. This quantification will be carried out for different experimental conditions which systematically alter the microenvironment of the regenerating axons. Specific Aims III-V focus on interactions of the regenerated axons with their target. The goal of these experiments is to establish how many axons grow back to their appropriate targets, and once in the target how many of them establish anatomical and physiological connections which are functional. Specific Aim VI will use the quantitative methods of the previous specific aims to directly compare the efficacy of various standard procedures for peripheral nerve repair. The results of these studies will provide quantitative baseline data concerning functional recovery following peripheral nerve repair. Direct correlation of anatomical and physiological measures of functional nerve regeneration will be used to compare the efficacy of different peripheral nerve repair strategies. Such quantitative comparisons have direct clinical relevance to human peripheral nerve repair.